title: IQGAP1 plays an important role in the cell proliferation of multiple myeloma via the MAP kinase (ERK) pathway.
abstract: The present study was designed to explore the role of IQ motif-containing GTPase activating protein 1 (IQGAP1) in the cell proliferation of multiple myeloma (MM) via the MAP kinase (ERK) pathway. Reverse transcription‑polymerase chain reaction (RT-PCR) and western blot analysis were carried out to evaluate the expression of IQGAP1 in RPMI8226, U266 and KM3 cell lines and in primary MM cells from 4 MM patients. shRNA-expressing plasmids were used in RPMI8226 cells to knock down IQGAP1 and an MTT assay was used to examine the proliferative activity of the RPMI8226-shIQGAP1 (clone 1), RPMI8226-shRNA negative and untransfected RPMI8226 cells in subgroups stimulated with VEGF/IL-6 or without. Western blot analyses were then performed to examine the protein levels of p-ERK1/2, ERK1/2, AKT, p-AKT, STAT3, p-STAT3 in the RPMI8226-shIQGAP1 (clone 1), RPMI8226-shRNA negative and untransfected RPMI8226 cells. Co-immunoprecipitation was used to verify the interaction between the IQGAP1 scaffold and the MAP ERK kinase. We found that IQGAP1 was overexpressed in the human myeloma cell lines and in the patient MM cells. The proliferation rate in the RPMI8226 cells was decreased when IQGAP1 was knocked down with shRNA. IQGAP1 was found to affect RPMI8226 cell proliferation by regulation of the MAP kinase (ERK1/2) pathway; IQGAP1 scaffold-MAP kinase (ERK) interaction was noted in the human myeloma RPMI8226 cell lines. In conclusion, IQGAP1 plays an important role in the cell proliferation of MM via the MAP kinase (ERK) pathway.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Ma
authors.forename: Zhouxiang
authors.initials: Z
authors.lastname: Jin
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.forename: Shujuan
authors.initials: S
authors.lastname: Zhou
authors.forename: Haige
authors.initials: H
authors.lastname: Ye
authors.forename: Songfu
authors.initials: S
authors.lastname: Jiang
authors.forename: Kang
authors.initials: K
authors.lastname: Yu
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics* / Q000378:metabolism; D009101:Multiple Myeloma / Q000235:genetics*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C508600:IL6 protein, human; C101203:IQ motif containing GTPase activating protein 1; D015850:Interleukin-6; D009363:Neoplasm Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020703:ras GTPase-Activating Proteins; D020929:Mitogen-Activated Protein Kinase Kinases